Natural killer T cells (NKT) are a unique lymphocyte population that expresses a T cell receptor (TCR) as well as NK lineage markers and possesses functional properties of both T and NK cells. Type I NKT cells, often called invariant NKT (iNKT) cells, express an invariant TCRα chain composed of a Vα14-Jα18 chain rearrangement in mice (Vα24-Jα18 in humans), that pairs preferentially with Vβ8.2, 7, and 2 (Vβ11 in humans). NKT cells are defined functionally by their ability to recognize glycolipid antigens presented in the context of the MHC class Ib molecule CD1 d. NKT cells bridge the gap between the innate and adaptive immune systems and are equipped to rapidly respond to stimuli to elicit an immune response.
When activated, iNKT cells rapidly produce large amounts of cytokines including interferon-γ (IFN-γ), IL-4 and IL-13, and the cytokine profile differs depending on the stimulus. α-galactosylceramide (α-GalCer) is the most extensively studied ligand for CD1d and is well established to be a potent stimulator of iNKT cells in both mice and humans. α-GalCer-stimulated iNKT cells produce high levels of IFN-γ and promote immunity against tumors as well as infectious pathogens. Multiple studies in murine tumor models have shown the ability of α-GalCer to induce anti-tumor immunity by iNKT- and IFN-γ-dependent mechanisms.
There still exists a need in the art to develop methods of NKT cell activation which may result in other ways to treat certain cancers, or induce immune responses.